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Development, Characterization, And Implementation Of An In Vitro Model Of Cerebrospinal Fluid Outflow Across The Arachnoid Granulations

Holman, David W.
http://rave.ohiolink.edu/etdc/view?acc_num=osu1218561491

Abstract Details

2008, Doctor of Philosophy, Ohio State University, Biomedical Engineering.
The arachnoid granulations (AGs) are herniations of the arachnoid membrane through the dura mater into the dural venous sinuses. They represent the final barrier between the cerebrospinal fluid (CSF) and venous blood and are involved in the return of CSF to the systemic venous circulation. Despite 125 years of study, our knowledge remains limited regarding the mechanism of fluid movement across the AGs. The location of the AGs within the cranial vault has made functional characterization of these structures difficult. In addition to their role in normal CSF turnover, the AGs may also play a role in disorders of CSF homeostasis. Of particular interest is idiopathic intracranial hypertension (IIH), where an increased intracranial pressure has been attributed to an increased resistance to CSF outflow, occurring at the AGs. The goal of this dissertation is to develop, characterize and implement an in vitro, model of CSF outflow across human AGs. This model can be utilized to study CSF outflow under normal and pathological conditions. This dissertation describes the culture and characterization of cells grown from human AG tissue. These AG cells expressed a unique immunological profile of cytoskeletal and junctional proteins that was maintained in culture. AG cells grown on permeable culture supports and perfused under pressures that mimic normal intracranial pressure showed a directionality of fluid transport that is consistent with the transport of CSF in vivo. Further, when fixed under pressure these cultured cells showed structures that are consistent with mechanisms of fluid transport described in intact AG tissue. Comparison of in vitro hydraulic conductivity values with known CSF parameters suggested that AG cells in culture can accurately represent the hydraulic conductivity of intact AG tissue in vivo. AG cells exposed to a physiological range of retinol concentrations, to replicate those seen in patients with primary IIH, showed no significant change in barrier integrity, indicating that retinol did not increase AG cell outflow resistance in culture. In summary, the results presented here demonstrate a working cell culture model of the CSF outflow pathway across the AGs that can be utilized to study CSF egress under normal and pathological conditions.
Deborah Grzybowski, PhD (Advisor)
Rita Alevriadou, PhD (Committee Member)
Mark Ruegsegger, PhD (Committee Member)
325 p.
Biomedical Research; Neurology; Ophthalmology
cerebrospinal fluid outflow; arachnoid granulations; in vitro model; idiopathic intracranial hypertension

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Citations

  • Holman, D. W. (2008). Development, Characterization, And Implementation Of An In Vitro Model Of Cerebrospinal Fluid Outflow Across The Arachnoid Granulations [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1218561491

    APA Style (7th edition)

  • Holman, David. Development, Characterization, And Implementation Of An In Vitro Model Of Cerebrospinal Fluid Outflow Across The Arachnoid Granulations. 2008. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1218561491.

    MLA Style (8th edition)

  • Holman, David. "Development, Characterization, And Implementation Of An In Vitro Model Of Cerebrospinal Fluid Outflow Across The Arachnoid Granulations." Doctoral dissertation, Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=osu1218561491

    Chicago Manual of Style (17th edition)

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This open access ETD is published by The Ohio State University and OhioLINK.